Vascular targeted photodynamic therapy is a promising cancer treatment modality by ablating tumor vasculature. The effectiveness of this treatment is often compromised by regrowth of endothelial cells, which causes tumor recurrence. In this preliminary report, we showed that activated PI3K signaling was involved in endothelial cell regrowth after PDT with verteporfin and combination between verteporfin-PDT and PI3K pathway inhibitor BEZ235 induced more cell apoptosis and greater inhibition in cell proliferation. These results suggest that rational combination of verteporfin-PDT and PI3K inhibitors result in enhanced treatment outcomes.
Photodynamic therapy (PDT) is a treatment modality in which cytotoxic reactive oxygen species are generated from
oxygen and other biological molecules when a photosensitizer is activated by light. PDT has been approved for the
treatment of cancers and age-related macular degeneration (AMD) due to its effectiveness in cell killing and
manageable normal tissue complications. In this study, we characterized the effects of verteporfin-PDT on SVEC
mouse endothelial cells and determined its underlying cell death mechanisms. We found that verteporfin was
primarily localized in mitochondria and endoplasmic reticulum (ER) in SVEC cells. Light treatment of
photosensitized SVEC cells induced a rapid onset of cell apoptosis. In addition to significant structural damages to
mitochondria and ER, verteporfin-PDT caused substantial degradation of ER signaling molecules, suggesting ER
stress. These results demonstrate that verteporfin-PDT triggered SVEC cell apoptosis by both mitochondrial and ER
stress pathways. Results from this study may lead to novel therapeutic approaches to enhance PDT outcome.
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